Peganum harmala plant is rich in effective compounds that have medicinal and pharmaceutical properties. The aim of this study was to investigate the effect of crude alkaloids extract of P. harmala seeds on histo-function of kidneys in rats. Sixteen adult male Wistar albino rats were divided equally into four groups, and treated intra-peritoneally for 30 days: Group I served as control, received water. Group II, group III, and Group IV received daily a single dose of 50, 100, and 200 mg/kg body weight of crude alkaloids of P. harmala; respectively. Blood biochemical markers of kidney functions were determined, and their sections were prepared for histological studies. Groups III and IV showed a significant increase in relative weights of kidneys. Both groups revealed a significant increase in the concentrations of creatinine and urea as compared to the control group. These findings were in consistency with histopathological examination of kidneys of treated rats. Lesions in the renal corpuscle included an increase in the space of the bowman capsule, vascular congestion, and necrosis in some glomeruli. Focal necrosis and vascular congestion were observed in cells lining the renal tubules, which might be the signs of beginning of the tumor in the cells lining the renal tubules. In conclusion, crude alkaloids extract of P harmala induced nephrotoxicity at higher doses in rats, and the plant cannot be used in human and animal nutrition.